This is an application for a Mentored Clinical Scientist Development (K08) award. The candidate is an infectious disease fellow at Massachusetts General Hospital. Her long term career goal is to become an independent investigator in the filed of infectious disease epidemiology. She is specifically interested in using the techniques of molecular epidemiology to study the transmission of tuberculosis. The accomplish this goal, the candidate is proposing to pursue didactic training in epidemiology and biostatistics as well as an intensive research experience at the Harvard School of Public Health under the mentorship of Dr. James M. Robins. She will also learn the methods of the molecular epidemiology of tuberculosis under the auspices of her co-sponsor Dr. Barry Bloom at the Albert Einstein College of Medicine. The research proposed in this application will use these methods to approach unresolved questions on transmission and the stain-specificity of virulence factors in tuberculosis. Specifically, the goals of this project are to 1. develop and test PCR-based methods to fingerprint tuberculosis infection is recent tuberculin skin test converters, 2. derive a quantitative estimate of TB transmission from an analysis of the genetic heterogeneity of the organism and 3. identify specific TB strains that differ in expression of virulence factors such as drug resistance, transmissibility and tissue tropism.